The skin is the largest organ in the human body and the cells which form the three skin layers are in a constant state of growth, with the outer layer of dead tissue being constantly shed. Replacement of cells from underlying layers is accomplished by cell division and maturation, the cells moving outward constantly at a rate that varies with age, sex, and other conditions.
An increased turnover of cells, where there is an increased rate of cell growth and cell death, is a common accompaniment of many conditions including injuries and disorders of various types. In the accompanying increased synthesis of all tissue components there is a strain placed upon the biosynthetic capacities of cells. A major component of the material which covers cells and occupies the spaces between them is glycosaminoglycans (GAG), which are by weight approximately half composed of amino sugars derived from N-acetyl glucosamine (NAG). In skin, about one-fifth of all the glucose utilized by the skin is destined for conversion to amino sugars.
A condition in which cell proliferation is increased up to ten times normal is psoriasis. This occurs in about 2 percent of the population (Harrison's Principles of Internal Medicine, 12th ed., Ch. 56, 1991), but with greater frequency in some groups (Idiopathic Inflammatory Bowel Disease, Thomson, A.B.R. ed., M.C.M. Printers, Ottawa, Ch. 23, 1982). Persons with inflammatory bowel disease have a higher incidence, about 15 percent. This group also has a higher incidence of joint disorders, about 25 percent. Both these conditions have been related to abnormalities in formation of glycosaminoglycans. Many patients with psoriasis have abnormal fingernails. Fingernails are composed mostly of chitin, which is a polymer of N-acetyl glucosamine (NAG), and thus fingernails are greater than 99 percent composed of NAG.
Several patents disclose amino sugars for treatment of disorders.
U.S. Pat. No. 4,590,067, May 20, 1986, Meisner, Peritain Ltd. discloses a composition for preventing and treating periodontal disease comprising bone meal, ascorbic acid, tyrosine and either glucosamine or cysteine. N-acetyl glucosamine is not disclosed.
French Pat. No. 2,473,887, Jul. 24, 1981, discloses the use of biochemical precursors of glucosamineglycans for the treatment of vascular disorders of functional or organic origin in which there is insufficient blood flow to the limbs, for asphyxic hypoxydotic symptoms, and in cosmetology, for skin defects caused by insufficient circulation to the skin. The precursors, which include N-acetylglucosamine, increase the elasticity of perivascular tissue, resulting in an increase in arterio-capillary blood flow, without having a vasodilating action.
U.S. Pat. No. 4,006,224, Feb. 1, 1977, J.F. Prudden, discloses the treatment of ulcerative colitis or regional enteritis in a mammal by administering D-glucosamine, or one of its salts. Equal or superior results to the conventional treatments of the two conditions are obtained. The dose is 20-300 mg/kg of D-glucosamine, HCl daily. In a clinical trial, a patient with Crohn's Disease that was not affected by ACTH or prednisone was given D-glucosamine, HCl subcutaneously. The symptoms stopped after several weeks of treatment.
WO A 702 244, N. Hendry, EP A 0178602, Peritain Ltd. and French Patent A 2016 182, Rotta Research Labratorium SpA, are of interest to this subject.
Hendry discloses a three-component preparation for tissue growth regulation comprising (a) at least one of N-acetyl-D-glucosamine or an oligomer thereof, or a deacylated derivative thereof, or a substituted product of these compounds; (b) at least one of biotin or an analog or derivative biotin, or biologically active residue thereof; and (c) a divalent metal cation together with a pharmaceutically acceptable anion.
Both Meisner and Hendry refer to amino sugars, including glucosamine and N-acetyl glucosamine. Their use is as one of a mixture of several other known nutrients, which have various effects on cell growth.
A key difference in the applicant's proposed use of NAG is this: It is proposed as a source of amino sugar for the synthesis of molecules such as glycoproteins and glycosaminoglycans, which are rich in NAG and the synthesis of which is stimulated by NAG.
NAG is formed from glucosamine and NAG is then directly converted into other amino sugars. NAG is thus a key substance, and in the applicant's work with intestinal tissue, it was found that the formation of NAG itself from glucosamine was the slow part of the process. This necessitates the use of NAG, specifically, and not a deacetylated form, or oligomer.
NAG, moreover, is more stable than glucosamine, is a neutral substance and is readily assimilated by tissues and utilized, whereas most oligomers are not.
The proposed use of NAG is unique and differs from existing art.
An article entitled "Decreased Incorporation of .sup.14 C-Glucosamine Relative to .sup.3 H-N-Acetyl Glucosamine in the Intestinal Mucosa of Patients with Inflammatory Bowel Disease", A.F. Burton and F.H. Anderson, vol. 78, No. 1, 1983, American Journal of Gastroenterology, discloses evidence that the synthesis of glycoproteins in intestinal mucosa of patients afflicted with inflammatory bowel disease is deficient in the diseased tissues of such patients. The article discusses possible reasons for the deficiency. However, no suggestions for alleviating the deficiency are made.